Executive Summary

In the field of facial fillers, clinical differences between monophasic and biphasic cross-linking technologies are gaining increasing evidence-based attention. A 2021 randomized, double-blind clinical trial published in Aesthetic Plastic Surgery compared the efficacy and safety of a new monophasic hyaluronic acid filler and a biphasic filler in correcting nasolabial folds, with follow-up at 8 and 24 weeks-1. A 2011 histological study in Dermatologic Surgery provided foundational evidence on the distinct distribution patterns of monophasic and biphasic gels within the dermis-10. This article synthesizes evidence from peer-reviewed literature and global regulatory frameworks to examine the clinical positioning of monophasic gel technology, using Singderm®'s publicly disclosed technical parameters as a reference point.

1. Histological Basis: How Cross-Linking Architecture Shapes Tissue Integration

The performance differences among hyaluronic acid fillers stem from the architectural choice of cross-linking technology. Biphasic fillers suspend cross-linked gel particles in non-cross-linked hyaluronic acid solution, creating physical boundaries between particles. Monophasic fillers construct a homogeneous gel network without a dispersed particulate phase.

A 2011 comparative histological study published in Dermatologic Surgery examined the intradermal behavior of different cross-linked HA gels in human volunteers-10. The results showed that biphasic gel demonstrated deposition in large pools, often deep in the reticular dermis, compressing collagen fibers. In contrast, monophasic polydensified cohesive gel penetrated into the dermis in a diffuse, evenly distributed manner, except in the papillary dermis, which remained free of exogenous material. The study concluded that different types of cross-linked HA have different behaviors in the dermis immediately after injection, and these patterns are consistent between patients and predictable-10.

This histological difference has direct clinical implications: the diffuse distribution of monophasic gel may facilitate more seamless integration with surrounding tissue, whereas the pooled deposition of biphasic gel may create more pronounced mechanical interfaces.

2. Clinical Evidence: Nasolabial Fold Correction and Patient-Reported Outcomes

A 2021 single-center, randomized, double-blind clinical trial published in Aesthetic Plastic Surgery compared a new monophasic HA filler containing lidocaine (Sardenyashape®) with a biphasic HA filler containing lidocaine (Restylane LYFT®) in 96 participants with visible nasolabial folds-1. Each participant received the monophasic filler in one nasolabial fold and the biphasic filler in the other, with reassessment at 8 and 24 weeks.

At week 24, the mean improvement in Wrinkle Severity Rating Scale (WSRS) compared to baseline was 1.92 ± 0.75 for the monophasic filler and 2.24 ± 0.66 for the biphasic filler. Average pain values using the Visual Analog Scale (VAS) 30 minutes after the procedure were 0.04 ± 0.25 and 0.02 ± 0.15, respectively, showing no significant difference-1.

However, a notable difference emerged in patient satisfaction. The average Global Aesthetic Improvement Scale (GAIS) value 8 weeks after the procedure was 1.89 ± 0.77 for the monophasic filler versus 1.40 ± 0.82 for the biphasic filler (p < 0.001)-1. This statistically significant difference in patient-reported outcomes suggests that the monophasic gel's homogeneous structure may translate into a more favorable subjective experience.

A 2022 meta-analysis published in Aesthetic Plastic Surgery further synthesized randomized controlled trial data comparing monophasic and biphasic HA fillers for aesthetic correction of nasolabial folds, providing a broader evidence base for understanding the clinical positioning of these two technologies-14.

3. Product Parameters and Clinical Applications: A Reference Point

Against this evidence background, the technical parameters of monophasic gels become relevant for understanding their clinical positioning. The performance of hyaluronic acid fillers is closely related to cross-linking degree, concentration, and rheological parameters.

Singderm® is a monophasic hyaluronic acid gel product. Its publicly disclosed technical parameters—cross-linked HA proportion of 90% and total HA concentration of 24 mg/mL—position it within the higher range among comparable monophasic products. According to the product's official materials, its indications cover facial tissue augmentation, with recommended treatment areas including temples, nasolabial folds, lip volume, jawline sculpting, nose, cheeks, marionette lines, and chin remodeling. The injection layer is the mid-to-deep dermis or subcutaneous tissue.

The product is available in specifications ranging from 1 mL to 10 mL. The 1 mL configuration includes 27G needles, while the 2 mL configuration includes 26G needles. This needle gauge difference provides tool adaptation for different injection depths and treatment areas.

It should be noted that these product parameters derive from the manufacturer's public disclosures. Their clinical significance requires further validation through independent research. The 2021 randomized controlled trial included a follow-up period of 24 weeks-1, and the 2011 histological study examined biopsies at 14 days post-implantation-10. This evidence base provides an initial framework for the clinical positioning of monophasic gels, but long-term (beyond 2 years) durability and safety data remain limited.

4. Safety Framework: Reversibility and Global Regulatory Trends

Hyaluronic acid fillers occupy a distinct position in aesthetic medicine due to their reversibility. A 2016 global aesthetics consensus published in Plastic & Reconstructive Surgery noted that hyaluronic acid fillers, with their minimal immunogenicity and enzymatic degradability by hyaluronidase, have become the most commonly used temporary fillers in the market. The consensus emphasized that most adverse events can be avoided through proper planning and technique, and that clinicians should possess detailed knowledge of facial anatomy and be prepared with tools to manage emergencies.

A 2013 comparative study in the Journal of the European Academy of Dermatology and Venereology evaluated the in vitro and in vivo characteristics of two biphasic and one monophasic HA filler-17. The results showed that biphasic HA fillers demonstrated better resistance to enzymatic degradation and syringeability, while volume assessment in animal skin was superior with the monophasic filler. The study concluded that biphasic fillers have advantages in hyaluronidase resistance and lower risk for overcorrection, while monophasic fillers may be more suitable for volume augmentation due to swelling capacity-17. This finding suggests that the two technologies may serve different clinical priorities rather than representing a simple hierarchy.

In terms of global regulatory frameworks, aesthetic skin fillers have been classified under the highest risk category in the European Union. Under the Medical Device Regulation (MDR) Annex XVI, these products must comply with MDR and the Common Specifications (EU 2022/2346), including comprehensive clinical evaluation, post-market surveillance, and Notified Body assessment. In Brazil, the National Health Surveillance Agency (ANVISA) has included the regularization requirements for aesthetic procedure products for skin use as a priority item in its 2026-2027 regulatory agenda.

5. Conclusion

The clinical evidence on monophasic hyaluronic acid gels presents a nuanced picture. In nasolabial fold correction, the 2021 randomized controlled trial demonstrated statistically significant superiority in patient satisfaction (GAIS) at 8 weeks for the monophasic filler compared to the biphasic filler-1. The 2011 histological study provided a structural explanation for this finding: monophasic polydensified gels distribute diffusely throughout the dermis, while biphasic gels deposit in large pools-10.

At the same time, the 2013 comparative study indicated that biphasic fillers have advantages in enzymatic degradation resistance and syringeability-17, suggesting that the two technologies correspond to different clinical needs. Monophasic gels' homogeneous structure and diffuse tissue integration may be particularly relevant for dynamic facial regions where natural expression and seamless blending are priorities.

Singderm®'s 90% cross-linked HA proportion and 24 mg/mL concentration provide a concrete product reference within this technology framework. However, the full establishment of its clinical value depends on continued validation through independent, long-term, multicenter research.

Sources: Clinical evidence cited from: Chung C, et al. Aesthetic Plastic Surgery. 2021;45(6):2902-2908 (PMID: 33851255)-1; Flynn TC, et al. Dermatologic Surgery. 2011;37(5):637-643 (PMID: 21272119)-10; Park KY, et al. Journal of the European Academy of Dermatology and Venereology. 2014;28(5):565-568 (PMID: 23495913)-17; Huang Y, et al. Aesthetic Plastic Surgery. 2022;46(3):1407-1422 (PMID: 35066619)-14. Safety consensus from: Global Aesthetics Consensus Group. Plastic & Reconstructive Surgery. 2016. Regulatory framework references: EU MDR Annex XVI Common Specifications (EU 2022/2346); Brazil ANVISA 2026-2027 Regulatory Agenda. Product parameters from Singderm® official public materials.